Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor α blockers.

OBJECTIVES: To evaluate prospectively the effect of weight loss on the achievement of minimal disease activity (MDA) in overweight/obese patients with psoriatic arthritis (PsA) starting treatment with tumour necrosis factor α (TNFα) blockers. METHODS: Among subjects with PsA starting treatment with TNFα blockers, 138 overweight/obese patients received a concomitant dietary intervention (69 a hypocaloric diet (HD) and 69 a free-managed diet (FD)). Changes in metabolic variables were measured and a complete clinical rheumatological evaluation was made in all patients at baseline and after a 6-month follow-up to define the achievement of MDA. RESULTS: 126 subjects completed the study. MDA was more often achieved by HD than by FD subjects (HR=1.85, 95% CI 1.019 to 3.345, p=0.043). A diet was successful (≥5% weight loss) in 74 (58.7%) patients. Regardless of the type of diet, after 6 months of treatment with TNFα blockers, ≥5% of weight loss was a predictor of the achievement of MDA (OR=4.20, 95% CI 1.82 to 9.66, p<0.001). For increasing weight-loss categories (<5%, 5-10%, >10%), MDA was achieved by 23.1%, 44.8% and 59.5%, respectively. A higher rate of MDA achievement was found in subjects with 5-10% (OR=3.75, 95% CI 1.36 to 10.36, p=0.011) and in those with >10% (OR=6.67, 95% CI 2.41 to 18.41, p<0.001) weight loss in comparison with those with <5% weight loss. CONCLUSIONS: Regardless of the type of diet, a successful weight loss (≥5% from baseline values) is associated with a higher rate of achievement of MDA in overweight/obese patients with PsA who start treatment with TNFα blockers.

Obesity and psoriatic arthritis: from pathogenesis to clinical outcome and management.

PsA is an axial and/or peripheral inflammatory arthritis associated with psoriasis, included in the group of spondylarthritides. It has been suggested that PsA could be a systemic disease, involving even coronary arteries and the heart. An increased prevalence of vascular risk factors has been found in PsA subjects as compared with the general population and psoriatic subjects. Moreover, PsA patients exhibit an increased prevalence of liver steatosis, a marker of metabolic syndrome, and of obesity. Interestingly, many reports demonstrate that adipose tissue is metabolically active, representing a source of inflammatory mediators, known as adipokines. The latter include TNF-α, macrophage chemoattractant protein-1, plasminogen activator inhibitor-1 (PAI-1), IL-6, leptin and adiponectin, leading to a pro-inflammatory status in obese subjects. This evidence supports the idea of obesity as a low-grade inflammatory disease. Accordingly, obesity might be associated with some rheumatic diseases. In particular, it seems to affect several features of PsA, such as its development, cardiovascular risk and clinical outcome. Recent data suggest that increased BMI in early adulthood increases the risk of PsA development in psoriatic patients, supporting a link between fat-mediated inflammation and joint involvement. Obesity may represent an additive cardio-metabolic risk factor in PsA subjects. Abdominal obesity may also determine an increased risk of not achieving minimal disease activity in PsA patients, highlighting the role of abdominal fat accumulation as a negative predictor of good clinical response to biologic agents. This review assesses the relationship between obesity and PsA according to the available literature.

Direct anticoagulant drugs to overcome limitations of vitamin K antagonists. A critical appraisal of data in atrial fibrillation patients.

INTRODUCTION: The usefulness of anticoagulation in patients with atrial fibrillation (AF) is well known. However, the inherent limitations of vitamin K antagonists (VKAs) have made the development of new oral anticoagulants necessary. Drugs directed against thrombin or the factor Xa are currently available. AREAS COVERED: These molecules, being administered at fixed doses and not requiring laboratory monitoring, overcome one crucial problem associated with the use of VKAs. However, data about the bleeding risk related to the use of these molecules should be further analyzed. EXPERT OPINION: The efficacy of direct anticoagulants (DACs) in AF-related stroke prevention has been considered the primary outcome in all Phase III published trials. On the other hand, the reduction of the bleeding risk is an important goal achieved by the DACs as compared with VKAs. Besides data deriving from randomized trials, when talking about new drugs, the need of evidences from the 'everyday clinical practice' are often requested. The aim of this literature revision is to report and analyze data from specific subgroups about which little is known. In particular, information about the use of DACs in oncologic patients, in patients receiving concomitant antiplatelet drugs and in the perioperative period is currently lacking. The parallel evaluation of all these data may lead to the identification of clinical and demographical criteria to choose when to switch to DACs.

Cardiovascular risk in rheumatic patients: the link between inflammation and atherothrombosis.

In addition to a high prevalence of the metabolic syndrome and a significant under-diagnosis of vascular risk factors (VRFs), the effect of chronic inflammation also represents the cornerstone of the raised cardiovascular (CV) risk in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Moreover, the finding that among current anti-inflammatory treatments, the use of tumor necrosis factor (TNF)-α blockers is associated with optimal rheumatologic and CV outcomes further supports the impact of inflammation on the CV risk. However, up-to-date treatment guidelines suggest that TNF-α blockers should be used only after the failure of traditional disease-modifying antirheumatic drugs (DMARDs). Early predictors of the therapeutic efficacy of traditional DMARDs are needed to identify candidates for TNF-α blocker treatment. Furthermore, whether the CV risk should be taken into account while choosing antirheumatic treatments is an emerging issue to be addressed. Common educational programs for specialists and general practitioners and appropriate CV prevention programs, taking into consideration traditional VRFs as well as the inflammatory status, should be planned to prevent ischemic events and to achieve optimal inflammation control in rheumatic patients.

Alcohol dosing and the heart: updating clinical evidence.

The consequences of heavy or irregular alcohol drinking have long been known. Recently, consistent information has been provided in support of an association between light/moderate alcohol consumption and protection from vascular and all-cause mortality, ischemic stroke, peripheral arterial disease, congestive heart failure, and recurrence of ischemic events. After reviewing the information with respect to major aspects of cardiovascular pathophysiology, to potential confounders and to underlying mechanisms, several concepts emerge. First, the recommended amounts of "safe alcohol drinking" in healthy individuals are up to two standard drinks (~20 g/d) for a man and up to one drink (10 g/d) for a nonpregnant woman. The overall balance for young premenopausal women, but not for older women, would be unfavorable for drinking. The risk of cancer would not outweigh potential benefits of alcohol on heart disease. Second, within the frame of a balanced pattern of dietary energy intake, patients with cardiovascular disease who drink alcohol should not exceed one or two standard drinks per day for women or up to two or three drinks per day for men. Third, the low rates of coronary heart disease among the Mediterranean people may be related to their pattern of drinking wine every day during meals. Regular drinking is associated with better outcomes than occasional (binge)/weekly drinking. Fourth, wine (ethanol with antioxidants) exhibits significantly higher anti-inflammatory effects than gin (ethanol without polyphenols), and thus in general wine should be preferred to liquor or beer.

Stroke prevention: from available antiplatelet drugs to novel molecular targets.

Stroke is the third most common cause of death in the industrialized countries and adequate primary and secondary prevention strategies are mandatory. In addition to lifestyle-changes and correction of cardiovascular risk factors, the mainstay of the atherothrombotic stroke prevention is represented by antiplatelet treatment. Although aspirin and thienopyridines have proved their efficacy in the prevention of arterial thrombotic events, limited efficacy, increased risk of bleeding, significant inter-individual variability in the response and extended duration of action that cannot be reversed if the need for haemostasis or emergency surgery arises represent major limitations of these drugs. Moreover, despite recommendations and guidelines about stroke prevention, registries data clearly suggest an underuse of antiplatelet drugs, mainly because of bleeding episodes fear. At variance with newer anticoagulant drugs, which showed a series of advantages as compared with the traditional warfarin treatment, newer antiplatelet drugs have only partially overcome these limitations. Although ad hoc studies on their efficacy in the stroke prevention are currently lacking, newer antiplatelet agents (mainly ticagrelor and prasugrel) do not provide a significant better protection over and above aspirin and/or clopidogrel in the prevention of atherothrombotic stroke. In addition, a significantly increased bleeding risk has been reported in subjects receiving these new thienopyridines. According to these data, the identification of further molecular targets is needed, in order to design future antiplatelet drugs. In this review, after summarizing major literature data about traditional and newer antiplatelet drugs, we will specifically focus on novel potential target candidates for antiplatelet therapy.

Improving the use of direct oral anticoagulants in atrial fibrillation.

The need for anticoagulation in patients with atrial fibrillation (AF), and the inherent limitations of warfarin have fostered the search for direct oral anticoagulant drugs (DOACs). In recent years, inhibitors of thrombin (Dabigatran etexilate) and of activated factor X (Rivaroxaban, Apixaban) have become clinically available, and current guidelines of the European Society of Cardiology recommend their use in AF patients. However, limitations and uncertainties as to their clinical handling have emerged. With the exception of those on Dabigatran, caution is presently recommended in patients undergoing ablation for AF, and in those who need dual antiplatelet treatment and/or invasive procedures. The use of DOACs is precluded in patients with (mechanical) heart valves, severe kidney or liver failure, malignancy, in those on prasugrel or ticagrelor, in those with the need for coronary stenting, and in naive patients with AF who need cardioversion. Moreover it must be borne in mind that limited long-term efficacy and safety data are available and that adherence of patients to DOACs may be a major issue in the real-life setting. The definition and type of monitoring to be employed to evaluate adherence to DOACs is lacking, nor have we practical guidelines on how to handle bleeding in patients on DOACs. Finally, ad hoc validated definitions of therapeutic failures are crucial in cost/utility analyses, but these are not available for DOACs. Thus, caution, vigilance and further clinical data are mandatory for a safe and appropriate use of DOACs as alternatives to warfarin in AF patients in real-life clinical settings.

Obesity and the prediction of minimal disease activity: a prospective study in psoriatic arthritis.

OBJECTIVE: We prospectively evaluated whether obesity impacts achievement of minimal disease activity (MDA) in subjects with psoriatic arthritis (PsA). METHODS: Among PsA subjects with an active disease and who were starting a treatment with tumor necrosis factor α blockers, 135 obese (body mass index [BMI] >30 kg/m(2) ) patients and 135 patients of normal weight (controls) were followed up for 24 months. At baseline and at the 12- and 24-month followup, all subjects underwent a clinical, rheumatologic, and laboratory assessment. RESULTS: With the exception of the prevalence of hypercholesterolemia and hypertriglyceridemia, case and control subjects were similar for all the clinical and demographic characteristics analyzed. At the 12-month followup, in both cases and controls, no significant changes in body weight were found (P > 0.05 for all). MDA was achieved by 98 (36.3%) of the 270 PsA individuals. The prevalence of obesity was higher in those that did not achieve MDA than in those that did (64.0% versus 25.5%; P < 0.001). After adjusting for all the other variables, obesity was associated with a higher risk of not achieving MDA (hazard ratio [HR] 4.90, 95% confidence interval [95% CI] 3.04-7.87; P < 0.001). The HR of not achieving MDA was 3.98 (95% CI 1.96-8.06, P < 0.001) and 5.40 (95% CI 3.09-9.43, P < 0.001) in subjects with first-degree (BMI <30 kg/m(2) ) and second-degree (BMI 30-35 kg/m(2) ) obesity, respectively. Among the 98 subjects who had achieved MDA at the 12-month followup, the presence of obesity was associated with a poor probability of sustained MDA at the 24-month followup (HR 2.04, 95% CI 1.015-3.61; P = 0.014). CONCLUSION: Obesity is a negative predictor of achieving and maintaining MDA.

[New oral anticoagulants: recommendations, precautions and perspectives for use]. / I nuovi anticoagulanti orali: raccomandazioni, precauzioni e prospettive d'uso.

In phase III studies, some oral inhibitors of both thrombin (dabigatran etexilate) and activated factor X (rivaroxaban, apixaban) have been employed as new anticoagulant drugs in patients with atrial fibrillation or acute coronary syndromes. Such new drugs have overcome a series of limitations of the standard-of-care warfarin, and argue for the possibility of an easy, widespread use of anticoagulation in vascular medicine. However, to this end, we need information on management of bleeding in patients receiving these drugs. Dabigatran etexilate, rivaroxaban and apixaban affect major laboratory tests for clotting. However, at present we do not know whether and how this information may be clinically useful. Their high cost is another major issue, and newer pharmacoeconomic studies are needed to evaluate their cost-effectiveness ratio vs warfarin.

Filling the gap between science & clinical practice: prevention of stroke recurrence.

Because of its high recurrence rate, active secondary prevention is mandatory once an episode of stroke has occurred. In non-cardioembolic stroke, in addition to lifestyle changes and to targeted treatments, current guidelines recommend aspirin, clopidogrel or aspirin+extended-release dipyridamole. In cardioembolic stroke (due to atrial fibrillation or flutter [AF]), vitamin K antagonists (VKAs) are recommended in most of patients. A favorable risk/benefit ratio of these treatments has been demonstrated also in elderly patients. However, registry data emphasize that such interventions are often under-used, especially in AF patients. A poor knowledge of current guidelines may play a role in hampering their application in clinical practice. The risk of major bleeding associated with antithrombotic drugs, their inherent limitations, such as socio-demographic (age >80 years, living alone) and clinical (previous or recent bleeding, trauma, cancer, dementia) features, may account for the gap between current guidelines for stroke/TIA prevention and clinical practice. The objective of the present report is to evaluate the gap between current recommendations/guidelines for stroke/TIA prevention and clinical practice (registry findings). In our opinion new antithrombotic drugs and detailed educational programs (especially devoted to general practitioners and to some medical specialists), concerning efficacy, safety and limitations of these strategies, are needed to better manage stroke epidemics in the third millennium.

Hepatic steatosis, carotid plaques and achieving MDA in psoriatic arthritis patients starting TNF-α blockers treatment: a prospective study.

INTRODUCTION: We prospectively evaluated whether hepatic steatosis (HS) and the presence of carotid plaques (CPs) impacts on achieving minimal disease activity (MDA) in psoriatic arthritis (PsA) patients starting tumor necrosis factor (TNF)-α blockers treatment. METHODS: Before starting treatment with TNF-α blockers, consecutive PsA subjects with an active disease were evaluated for the presence of the metabolic syndrome (MetS), HS and CPs. The incidence of MDA was evaluated 12 and 24 months later. RESULTS: Among 270 PsA subjects, 91 (33.7%) exhibited the MetS, 58 (21.5%) CPs and 76 (28.1%) HS. At the 12-month follow-up, 98 (36.3%) individuals achieved MDA. Compared with those who did, a higher prevalence of the MetS, HS and CPs was found in subjects who did not achieve the MDA (P always < 0.001). After adjusting for the MetS and for all the other demographic/clinical characteristics analyzed, the presence of HS and CPs at baseline independently predicted the risk of not achieving MDA (Hazard Ratio: 1.91, 95% confidence interval (CI): 1.04 to 3.38, P = 0.035 and Hazard Ratio: 3.21, 95%CI: 1.64 to 6.29, P = 0.001, respectively). Separate Kaplan-Meier survival models confirmed this (Log-Rank: 12.894, P < 0.001 and Log-Rank: 12.849, P < 0.001, respectively). Compared with those without, progressively increasing Hazard Ratios of not achieving MDA were found in those with HS, CPs or HS + CPs at baseline. Moreover, the presence of HS and/or CPs predicted the risk of relapse during the additional 12-month follow-up (Hazard Ratio: 2.85, 95%CI: 1.27 to 6.37, P = 0.011 and Hazard Ratio: 3.17, 95%CI: 1.57 to 6.41, P = 0.001 respectively). CONCLUSIONS: HS and/or CPs at baseline are negative predictors of achieving and maintaining MDA.

Predictors of early minimal disease activity in patients with psoriatic arthritis treated with tumor necrosis factor-α blockers.

OBJECTIVE: To identify predictors of early minimal disease activity in patients with psoriatic arthritis (PsA) receiving tumor necrosis factor-α (TNF-α) antagonists. METHODS: In total 146 consecutive patients with PsA eligible for anti-TNF-α therapy were enrolled. At baseline (T0) information about age, sex, PsA subset, disease duration, comorbidities, and treatments was collected. All subjects were tested for metabolic syndrome (MetS) and/or liver steatosis. A clinical and laboratory evaluation was performed at T0 and at 3 months (T3). Changes in all these variables were compared in subjects achieving minimal disease activity (MDA) and those who did not. RESULTS: Among 146 PsA subjects, 10 discontinued therapy before 3-month followup because of adverse events; thus 136 concluded the study. All clinical outcome measures changed significantly from T0 to T3. Erythrocyte sedimentation rate showed a significant reduction (p < 0.001). C-reactive protein (CRP), serum cholesterol, and triglycerides showed no significant variation (p > 0.05). The prevalence of MetS and liver steatosis showed no significant differences between subjects achieving MDA and those who did not (p = 0.347 and 0.053, respectively). Patients achieving MDA at T3 were younger than those not achieving MDA (p = 0.001). A lower baseline tender joint count (p = 0.001), swollen joint count (p = 0.013), Bath Ankylosing Spondylitis Disease Activity Index (p = 0.021), and Ritchie index (p = 0.006) were found in subjects achieving MDA. Age (OR 0.896, p = 0.003) and Bath Ankylosing Spondylitis Functional Index (BASFI) (OR 0.479, p = 0.007) inversely predicted, whereas CRP (OR 1.78, p = 0.018) directly predicted, achievement of MDA at T3. CONCLUSION: In patients with PsA, age, CRP, and BASFI at the beginning of treatment were found to be reliable predictors of MDA after 3 months of TNF-α blocker therapy.

Hepatic steatosis and disease activity in subjects with psoriatic arthritis receiving tumor necrosis factor-α blockers.

OBJECTIVE: Little is known about tumor necrosis factor-α (TNF-α) blockers, disease activity, and liver steatosis (hepatic steatosis; HS) in subjects with psoriatic arthritis (PsA). We prospectively evaluated changes in HS during treatment with TNF-α blockers. METHODS: In 48 patients with PsA who had evidence of HS before the beginning of TNF-α blocker treatment, an ultrasound followup examination was performed after a 12-month treatment period with TNF-α blockers. All subjects were stratified according to minimal disease activity (MDA) or not (n-MDA), during treatment with TNF-α blockers. Changes in grade of HS were evaluated in parallel in 42 controls with HS and without PsA. RESULTS: At baseline, no significant difference in HS score was found between PsA subjects and controls (HS scores 1.46 ± 0.65 vs 1.62 ± 0.66, respectively; p = 0.249). At 12-month followup, a worsening HS score was found in 20 (41.7%) patients with PsA and in 6 (14.3%) controls (p = 0.005). Overall, the grade of HS worsening was higher in patients with PsA (0.37 ± 0.70) than in controls (0.09 ± 0.43; p = 0.028). A significantly lower prevalence of worsening HS was found among patients with PsA with MDA, compared with n-MDA subjects (16.7% vs 66.7%, respectively; p = 0.001). Laboratory measures of liver function behaved similarly. The risk of worsening HS in patients with PsA who had MDA was similar to that in controls (HR 1.20, 95% CI 0.34-4.33, p = 0.77), and higher in patients who did not have MDA (HR 4.46, 95% CI 1.73-11.47, p = 0.001, regression analysis). CONCLUSION: Compared with patients with MDA, those with active disease after 12-month treatment with TNF-α blockers exhibited significantly higher incidence of worsening liver steatosis.

Aspirin resistance, platelet turnover, and diabetic angiopathy: a 2011 update.

In 2004 an editorial article on the so-called "aspirin resistance" and diabetic angiopathy as related to platelet turnover was published by one of us. An update of this issue is now presented. The evidence of an incomplete inhibition of platelet function by aspirin, despite doses of the drug proved to be clinically effective are employed, was first reported in the '80s, in studies devoted to platelet turnover. Based on this concept, the possibility of monitoring the entry of newly formed platelets into the circulation after aspirin ingestion was documented by measuring the return of thromboxane biosynthesis by platelets challenged in vitro by pairs of aggregating agents. The data obtained showed that platelets with intact cyclooxygenase activity could be detected into the circulation of control individuals as early as 4-6hrs after aspirin ingestion, but at shorter time intervals in diabetic angiopathy. In the latter setting, it was concluded that "schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, presumably because these patients have a high rate of entry of new platelets into the circulation". As many as 25years after its original publication, the clinical relevance of an accelerated platelet turnover as to "aspirin resistance" has been confirmed and extended to other clinical settings at high risk of ischemic events. Newer aspirin dosing and scheduling, tailored at reducing the individual patient risk related to an incomplete inhibition of platelet function by a standard aspirin dose should now be defined.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor (PPAR) α, PPARγ, sterol regulatory element-binding protein-1, carbohydrate responsive element-binding protein], impacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil, flaxseeds, olive oil) which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

New anti-thrombotic drugs for stroke prevention.

Ischemic stroke is the third most common cause of death and of long-term disability and exhibits a high recurrence rate. Therefore, appropriate primary and secondary prevention is mandatory. In non-cardioembolic stroke, in addition to lifestyle changes and to targeted treatments, current guidelines recommend antiplatelet treatment. In cardioembolic stroke, Vitamin K antagonists (VKAs) are recommended. Although a favorable risk/benefit ratio of both treatments has also been demonstrated in elderly patients, registry data emphasize that such interventions are often under-used, especially in patients with atrial fibrillation (AF). Furthermore, variability in the inter-individual response to drugs has been recognized as a leading cause of event recurrence. Thus, in addition to poor adherence, efficacy and safety issues appear to be involved in the recurrence rate of stroke. In this review, we report main Registries data on adherence to stroke prevention treatment schedule. We also discuss the major limitations of "traditional" antithrombotic drugs and report Phase III study results on safety and efficacy of new antiplatelet and anticoagulant drugs, with emphasis on stroke prevention.

Assessing joint involvement in haemophilia by clinical rheumatologic scores. A pilot study on similarities with subjects with psoriatic arthritis.

Because of joint haemorrhages, severe haemophilia subjects often have limitations in their daily activities. Current orthopaedic scores (OJS) in haemophilia miss mild joint impairments and only pick up severe alterations. Twelve young severe haemophiliacs (20.25 ± 1.9 years of age), were evaluated for OJS as well as for indices employed in rheumatoid arthritis [28-joint Disease Activity Score (DAS-28), Ritchie index, Health Assessment Questionnaire (HAQ), visual analogue scale (VAS)], spondyloarthritis [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), HAQ, VAS] and osteoarthritis [Knee injury and Osteoarthritis Outcome Score (KOOS), VAS]. Twenty-four matched apparently healthy subjects and 29 subjects with psoriatic arthritis (PsA) with oligoarticular involvement (one to three swollen joints) served as controls. In addition to the impairment of target joints (elbow, in five of five in those on-demand treatment; three, elbows; four, knee in those on secondary prophylaxis), HAQ (mean 0.71 ± 0.95) and VAS (3.12 ± 2.36) documented a quality of life and a perception of pain in haemophiliacs similar to that of PsA subjects (p = 0.061 and p = 0.063, respectively). Their Ritchie index did not differ from that of subjects with psoriatic arthritis (5.75 ± 8.1 vs 7.73 ± 9.22; p = 0.408), nor did the BASDAI score with respect to psoriatic arthritis patients (p = 0.105). Six of 12 haemophiliacs (50%) had KOOS values from 70 to 50 (significant function joint impairment); 3 of 12 (25%) showed DAS-28 values >3.2 (moderate disease activity), 2 of 12 (16.6%) severe disease activity (>5.1). All these indices significantly correlated with VAS and HAQ in haemophilia subjects. A rheumatologic assessment may help identify early polyarticular disease and subclinical abnormalities involving joints not usually studied (not target joint) in haemophiliacs. These pilot data provide the rationale for testing a systemic involvement in haemophiliacs by means of high-tech imaging and to start early-onset prophylaxis/treatment in this setting.

Exploring newer cardioprotective strategies: ω-3 fatty acids in perspective.

In the 1980s, observational retrospective studies showed an inverse relation between coronary heart disease (CHD) and consumption of fish containing fatty acids that belong to the omega (ω)-3 family. Large case-control studies and prospective intervention trials consistently showed that ω-3 fatty acids supplementation lowers fatal myocardial infarction (MI) and sudden cardiac death. By analysing the strengths of the results of individual studies and how the meta-analyses agree with them, putting together relevant backgrounds, and identifying open questions, the following findings/directions emerge. (i) Dietary and non-dietary intake of ω-3 fatty acids reduces overall mortality, mortality due to MI, and sudden death in patients with CHD; (ii) Fish oil consumption directly or indirectly affects cardiac electrophysiology. Fish oil reduces heart rate, a major risk factor for sudden death; (iii) Among patients with implantable cardioverter defibrillators, ω-3 fatty acids do not reduce the risk of ventricular tachycardia/ventricular fibrillation and may actually be pro-arrhythmic; (iv) The consumption of ω-3 fatty acids leads to a 10-33% net decrease of triglyceride levels. The effect is dose-dependent, larger in studies with higher mean baseline triglyceride levels, and consistent in different populations (healthy people, people with dyslipidaemia, diabetes, or known cardiovascular risk factors); (v) Outcomes for which a small beneficial effect ω-3 fatty acids is found include blood pressure (about 2 mmHg reduction), re-stenosis rates after coronary angioplasty (14% reduction), and exercise tolerance testing. Major experimental data provide strength (biological plausibility) for these findings, and define directions for newer clinical trials with ω-3 fatty acids.